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Biology subjects

Remo Rohs

Publications and source records attributed to Remo Rohs.

2 recordsLinked to original sources

Human enhancers associated with immune response harbour specific sequence composition, activity, and genome organization

The FANTOM5 consortium recently characterized 65,423 human enhancers from 1,829 cell and tissue samples using the Cap Analysis of Gene Expression technology. We showed that the guanine and cytosine content at enhancer regions distinguishes two classes of enhancers harboring distinct DNA structural properties at flanking regions. A functional analysis of their predicted gene targets highlighted one class of enhancers as significantly enriched for associations with immune response genes. Moreover, these enhancers were specifically enriched for regulatory motifs recognized by TFs involved in immune response. We observed that enhancers enriched for links to immune response genes were more cell type specific, preferentially activated upon bacterial infection, and with specific response activity. Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically-associated domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.

Genomics

ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo

Chromatin endogenous cleavage (ChEC) uses fusion of a protein of interest to micrococcal nuclease (MNase) to target calcium-dependent cleavage to specific genomic loci in vivo. Here we report the combination of ChEC with high-throughput sequencing (ChEC-seq) to map budding yeast transcription factor (TF) binding. Temporal analysis of ChEC-seq data reveals two classes of sites for TFs, one displaying rapid cleavage at sites with robust consensus motifs and the second showing slow cleavage at largely unique sites with low-scoring motifs. Sites with high-scoring motifs also display asymmetric cleavage, indicating that ChEC-seq provides information on the directionality of TF-DNA interactions. Strikingly, similar DNA shape patterns are observed regardless of motif strength, indicating that the kinetics of ChEC-seq discriminates DNA recognition through sequence and/or shape. We propose that time-resolved ChEC-seq detects both high-affinity interactions of TFs with consensus motifs and sites preferentially sampled by TFs during diffusion and sliding.

Genomics